Data from A Phase II Trial of Hu14.18K322A in Combination with Induction Chemotherapy in Children with Newly Diagnosed High-Risk Neuroblastoma
Year: 2023
Type: other
Abstract: Purpose: We sought to evaluate whether combining a humanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma. Patients and Methods: We conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte–macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoin were then administered. Secondary outcomes included reduced tumor volume and semiquantitative 123I-metaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction. Results: Forty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6–88.0]. This was accompanied by primary tumor volume reductions (median, –76%; range, –100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9–93.3). Conclusions: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.
Authors: Wayne L. Furman, Sara M. Federico, Mary Beth McCarville, Barry L. Shulkin, Andrew M. Davidoff, Matthew J. Krasin, Natasha Sahr, April Sykes, Jianrong Wu, Rachel C. Brennan, Michael William Bishop, Sara Helmig, Elizabeth Stewart, Fariba Navid, Brandon Triplett, Victor M. Santana, Armita Bahrami, Gwendolyn Anthony, Alice L. Yu, Jacquelyn Hank, Stephen D. Gillies, Paul M. Sondel, Wing H. Leung, Alberto S. Pappo
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4361958488